拉米呋啶治疗后乙肝病毒聚合酶YMDD变异.doc

拉米呋啶治疗后乙肝病毒聚合酶YMDD变异 　 作者：王亚文，马列婷，惠凌云，谭巩诚，胡志国，王富中 【关键词】 拉米呋啶；乙肝病毒；YMDD变异 　　摘要：目的 观察拉米呋啶治疗慢性乙肝患者1年前后，患者体内HBV DNA多聚酶结构域C的酪氨酸―甲硫氨酸―天门冬氨酸―天门冬氨酸(YMDD)基因变异情况，及其与血清HBV DNA、丙氨酸氨基转移酶(ALT)水平及乙肝标志物变化的关系。方法 采用实时荧光定量PCR、ELISA及速率法分别检测60例乙肝患者经拉米呋啶治疗后其血清YMDD、HBV DNA、乙肝标志物及ALT的变化情况。结果 拉米呋啶治疗9月、1年后YMDD的变异率分别为5%、13.3%。YMDD变异组HBV DNA阴转率为12.5%，无变异组HBV DNA阴转率为67.3%，两组阴转率相比差异有统计学意义(Plt;0.01)。拉米呋啶治疗1年后YMDD变异组ALT为(40.7±14.7)u/L，无变异组ALT为(26.5±10.1)u/L，两组相比差异有统计学意义(Plt;0.01)。 5名HbeAg阴转患者无YMDD变异。结论 乙肝患者经拉米呋啶治疗后，YMDD变异率随用药时间的延长可逐渐增加，当其HBV DNA、ALT含量出现明显反跳时，应及早改变治疗方案。 　　关键词：拉米呋啶；乙肝病毒；YMDD变异 　　Mutation of YMDD in hepatitis B virus polymerase　after lamivudine treatment 　　ABSTACT: Objective To investigate tyrosinemethionineaspartateaspartate (YMDD) mutation and the relationship with the levels of HBV DNA, ALT and HbeAg in chronic hepatitis B patients after one year of lamivudine therapy. Methods The serum YMDD mutation, HBV DNA, ALT and HbeAg levels of 60 patients on lamivudine therapy were detected by FQPCR, ELISA, and rate method, respectively. Results The occurrence of mutation in the patients was 3.3% and 13.3%, respectively after 9month and oneyear treatment with lamivudine. There was significance difference in the transnegative ratios of HBV DNA between the patients with and without YMDD mutation (Plt;0.01). The levels of ALT in the patients with YMDD mutation and without YMDD mutation were (40.7±14.7)u/L and (26.5±10.1)u/L, respectively. The level of ALT in patients with YMDD mutation was higher than that in the patients without YMDD mutations. There was no YMDD mutation in the 5 patients whose HbeAg resurned negative. Conclusion After lamivudine therapy, patients with YMDD mutation showed significant decrease in the level of HBV DNA and ALT. 　　KEY WORDS:lamivudine; hepatitis B virus; YMDD mutation 　　拉米呋啶(lamivudine)是一种能抑制乙型肝炎病毒(HBV)复制的核苷类药物[1]，但在长期的用药过程中，部分患者出现耐药。患者体内HBV DNA多聚酶结构域C的酪氨酸―甲硫氨酸―天门冬氨酸―天门冬氨酸(tyrosinemethionineaspartateaspartate, YMDD)基因发生变异[2]，其变异主要有两种形式：HBV的P基因C区密码子甲硫氨酸突变为缬氨酸(Y